The chicken oviduct also referred to as a “Fallopian tube” is an organ for secreting several proteins, such as ovalbumin, in which proliferation and differentiation of cells occur periodically. In particular, it is reported that the oviduct wall of an ovipara secretes nutritive elements and an eggshell to feed to an egg, and the oviduct of a chicken secretes protein to accumulate with a large amount in the egg (Modern Poultry Science, Bong-Kug OHH, 1988).
In general, an egg is a food abundant of nutritive elements such as proteins, vitamin A, cholesterol and inorganic matters, and has excellent nutritive values with the protein content about twice of that of milk and the fat content higher than those of milk, cheese and beef. It is also reported that the egg has functional properties such as immunologic enhancement and remedial value. Particularly, it is reported that the white of the egg acts as an antidote when a toxic substance and/or an irritant substance is taken in and also protects the gastric and intestinal mucosa, thereby preventing the same from an ulcer. Accordingly, the consumption of eggs is sharply rising in the recent days, and there is increasing interest on the development of methods of producing functional eggs that contain new functional contents useful for the human body. Of various conventional methods, which have been developed in relation with the foregoing, Korean Patent Application Publication No. 2006-0030186 discloses a method of producing eggs with increased taurine content by breeding layer chickens with a feed to which feather meal and pyridoxine are added. Korean Patent Application Publication No. 2003-0082207 discloses a method of producing mineral-activated salicomia herbacea eggs by adding salicomia herbacea into a general formula feed, by which the eggs include a large amount of minerals, such as Mg, Ca, K, Fe, P, I, Na and salts, which are contained in the sea. Furthermore, Korean Patent No. 0567311 discloses a method of producing special eggs using a layer chicken feed composition, which includes aloe contents. The conventional methods of producing functional eggs are in consideration that specific nutritive elements in the white and the yellow can increase in proportion to the amount of specific elements added to a formula feed for chickens. However, these methods have a drawback in that the incidental expense of the additives increases in addition to the expense of the formula feed.
Accordingly, there are new approaches to produce functional eggs based on the development of genetic engineering. Particularly, of these approaches, studies on a transgenic chicken are on the limelight. That is, various studies are being carried out in many countries in order to develop chickens that lay eggs containing genetic material useful for the human body. Genetic engineering technologies, which have been used to produce the transgenic chicken up to date, include a method of producing the transgenic chicken using a vector, which includes a gene expressing a useful protein (Harvey A. J. et al., Nature Biotechnology, 20: 396-399, 2002) and methods of producing a useful protein in the chicken using a promoter (Harvey A. J. & Ivarie R., Poultry Science 82: 927-930, 2003; Chen Y. X., Mol. Vis. 17: 874-883, 2004). Especially, as the method of using a promoter, some methods using cytomegalovirus (CMV) promoter and/or ovalbumin promoter have been developed. However, since the CMV promoter is randomly expressed in the whole body, expression control is difficult and the CMV promoter may change the physiological phenomena of the chicken. On the contrary, the ovalbumin promoter can be specifically expressed in the chicken oviduct and the egg to tissue-specifically induce the expression of protein, thereby minimizing the abnormal physiological phenomena of the chicken. However, since the ovalbumin promoter is patented by foreigners, even if the transgenic chicken using the ovalbumin promoter is produced, its industrialization is not easy at all. Furthermore, only a minimum number of examples produce a tissue-specific transgenic chicken using the ovalbumin promoter.
Accordingly, it is required to find a novel gene and a promoter, which are tissue-specifically expressed without taking a great effect on the physiological phenomena of chickens, in order to produce functional eggs, transgenic chickens that can lay the functional eggs, and proteins useful to the human body from the transgenic chickens.
The present inventors have studied to find a novel promoter, which induces tissue-specific expression in order to produce functional eggs and transgenic chickens which can lay the functional eggs. As a result, the present inventors found out a promoter region of the AGR2 gene which is oviduct-specifically expressed, and succeeded in producing a recombinant expression vector including the promoter region, thereby completing the present invention.